A PKC-Sp1 signaling pathway induces early differentiation of human keratinocytes through upregulation of TSG101

Huey Ling You, Hock Liew Eng, Shih Fang Hsu, Ching Mei Chen, Tzung Cheng Ye, Wei Ting Liao, Man Yi Huang, Richard Baer, Jiin Tsuey Cheng*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

14 Scopus citations


The TSG101 protein has been implicated in multiple biological functions including regulation of gene transcription, vesicular trafficking, cellular growth and differentiation. However, the cellular signals that control TSG101 functions are unclear. Here, we demonstrate that TSG101 is upregulated during keratinocyte differentiation in both human foreskin tissue and reconstructed organotypic skin cultures. In addition, we found that TSG101 siRNA inhibits calcium-induced early differentiation of human foreskin keratinocytes, indicating an essential and downstream role for TSG101 in this process. Furthermore, the PKC agonist TPA promotes expression of TSG101 and keratin 10 in keratinocytes under low calcium conditions, while co-treatment with the PKC inhibitor GF 109203X blocks TPA-induced TSG101 and keratin 10 upregulation. Previous work has established that the TSG101 gene is controlled by a TATA-less promoter that harbors a Sp1-binding site. Here we show that both calcium and TPA activate PKC, stimulate phosphorylation of Sp1, and augment the activity of the TSG101 promoter in a manner dependent on its Sp1-binding site. Release of calcium from intracellular stores with thapsigargin, an endoplasmic reticulum Ca2+-ATPase inhibitor that elevates intracellular free Ca2+ without activating PKC, does not affect Sp1 phosphorylation and TSG101 promoter activity. Taken together, these data suggest that an intracellular calcium store independent PKC-Sp1 signaling pathway induces early keratinocyte differentiation through upregulation of TSG101.

Original languageEnglish
Pages (from-to)1201-1211
Number of pages11
JournalCellular Signalling
Issue number6
StatePublished - 06 2007
Externally publishedYes


  • Calcium
  • Differentiation
  • Keratinocyte
  • PKC
  • Sp1
  • TSG101


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